CN105267283B - Pharmaceutical composition for reducing blood fat and preparation method thereof - Google Patents
Pharmaceutical composition for reducing blood fat and preparation method thereof Download PDFInfo
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Abstract
The invention provides a pharmaceutical composition with the effect of reducing blood fat, which is prepared from 160 parts by weight of red yeast powder 130-160 parts, 65-80 parts by weight of eucommia seed oil, 13-16 parts by weight of propolis, 1110 parts by weight of pseudo-ginseng 880-1110 parts or pseudo-ginseng extract equivalent to the crude drug amount of pseudo-ginseng and pharmaceutically acceptable auxiliary materials. The invention also discloses a preparation method of the pharmaceutical composition. Animal pharmacodynamic tests prove that the pharmaceutical composition has better blood fat reducing effect.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a pharmaceutical composition with a blood fat reducing effect.
Background
In recent years, there are many drugs, health foods, foods and other products which have been researched or marketed and have the effect of reducing blood lipid, wherein the traditional Chinese medicine or the traditional Chinese medicine compound with the effect of reducing blood lipid is many-number, but the antagonistic effect brought by the difference of the active ingredients of different traditional Chinese medicines and the side effect generated by some traditional Chinese medicines lead to the rare, high-efficiency and safe pharmaceutical composition products.
In recent years, more research and development are carried out on eucommia seed oil and red yeast rice, and part of products are publicized to be hotter. The oil content of the eucommia seed is about 30 percent, and the eucommia seed oil is rich in alpha-linolenic acid. The red yeast has complex components, and most published researches show that the lovastatin serving as a main blood fat reducing active component has a small proportion in the red yeast. The inventor finds that the compound of red yeast rice, eucommia seed oil and the like has very large difference in blood fat reduction caused by different compatibility compositions in the research process, and the application of the medicinal composition for reducing the blood fat effect, which is prepared by taking the red yeast rice, the eucommia oil, the pseudo-ginseng and the propolis as main raw materials, is not disclosed and reported after years of research and comparison.
Disclosure of Invention
One object of the present invention is to provide a pharmaceutical composition with hypolipidemic effect; the invention also aims to provide a preparation method of the pharmaceutical composition.
The purpose of the invention is realized by the following technical scheme:
the inventor provides a blood fat reducing pharmaceutical composition, which is prepared from the following raw materials in parts by weight and pharmaceutically acceptable auxiliary materials:
160 parts of red yeast powder 130-80 parts, 65-80 parts of eucommia seed oil, 13-16 parts of propolis, 1110 parts of pseudo-ginseng 880-1110 parts or pseudo-ginseng extract equivalent to crude drug quantity of pseudo-ginseng, wherein the red yeast is fine powder of red yeast, the red yeast is in accordance with Chinese medicinal material standard (2009 edition) in Hunan province, the lovastatin content in the red yeast powder is 0.4-0.6%, the alpha-linolenic acid content in the eucommia seed oil is 55-75%, the pseudo-ginseng and the propolis are in accordance with the regulation under the 2010 edition of Chinese pharmacopoeia, and the pseudo-ginseng extract is an extract obtained by extracting the pseudo-ginseng with water or an alcohol extraction method or an extract obtained by refining the crude extract by macroporous resin.
The raw materials of the pharmaceutical composition may be further preferably: 150 parts of red yeast powder 140, 70-75 parts of eucommia seed oil, 14-15 parts of propolis, 1050 parts of pseudo-ginseng 970 or pseudo-ginseng extract equivalent to crude drug amount of the pseudo-ginseng, wherein the lovastatin content in the red yeast powder is 0.4-0.6%, the alpha-linolenic acid content in the eucommia seed oil is 55-75%, the pseudo-ginseng and the propolis accord with the regulation of Chinese pharmacopoeia 2010 edition, and the pseudo-ginseng extract is an extract obtained by extracting pseudo-ginseng with water or an alcohol or refining the crude extract by macroporous resin.
The raw materials of the pharmaceutical composition can be further preferably: 146.4 parts of red yeast powder, 73.2 parts of eucommia seed oil, 14.4 parts of propolis, 1000 parts of crude panax notoginseng or a panax notoginseng extract equivalent to the crude drug amount of the panax notoginseng, wherein the lovastatin content in the red yeast powder is 0.45-0.55%, the alpha-linolenic acid oil content in the eucommia seed oil is 60-70%, the panax notoginseng and the propolis accord with the regulation of Chinese pharmacopoeia 2010, and the panax notoginseng extract is an extract obtained by extracting panax notoginseng with water or an alcohol or an extract obtained by refining the crude extract by macroporous resin.
The eucommia seed oil in the medicinal composition is eucommia seed oil obtained by any one of the following methods or a mixture of several types of eucommia seed oil:
(1) microwave extraction: crushing eucommia ulmoides seeds to 30-60 meshes, adding an extracting agent with the weight of 5-10 times, extracting for 10-20 min at the extraction temperature of 20-40 ℃ by microwave power of 600-800 w, and removing the extracting agent from an extract through reduced pressure distillation, wherein the extracting agent is cyclohexane or normal hexane or acetone or petroleum ether;
(2) supercritical carbon dioxide extraction: pulverizing eucommia ulmoides seeds to 30-60 meshes, extracting under the pressure of 30-40 MPa and CO2The flow is 20-40 kg/h, the extraction temperature is 15-35 ℃, the extraction time is 1-3 h, the separation pressure is 8-10 MPa, and the separation temperature is 40-50 ℃;
(3) squeezing semen Eucommiae at room temperature, and filtering;
(4) washing the crude oil obtained by the method (1), (2) or (3), dehydrating, degumming, dewaxing, decolorizing, deacidifying, deodorizing and refining.
The refining process of the crude oil obtained in the above method (1) or (2) or (3) for preparing eucommia seed oil is a conventional method, and comprises a separation method by using an ultrafiltration membrane.
The pseudo-ginseng extract in the pharmaceutical composition is an extract obtained by any one of the following methods or a mixture of several extracts:
(1) reflux-extracting the pseudo-ginseng coarse powder for 1-3 times by using 4-10 times of 40-75% methanol or ethanol by weight, wherein each time lasts for 1-3 hours, combining ethanol extract, removing ethanol, concentrating and drying;
(2) reflux-extracting the pseudo-ginseng coarse powder for 1-3 times by using 40-75% methanol or ethanol with the weight being 4-10 times of that of the pseudo-ginseng coarse powder, wherein each time lasts for 1-3 hours, merging ethanol extract, removing alcohol, adsorbing by using macroporous resin, eluting by using water until no purple ring reaction occurs in effluent water, eluting by using 70-90% ethanol, collecting eluent, concentrating and drying;
(3) extracting the pseudo-ginseng coarse powder with 4-10 times of water for 1-3 times, each time for 1-3 hours, combining water extract, concentrating and drying;
(4) extracting the pseudo-ginseng coarse powder with 4-10 times of water for 1-3 times, each time for 1-3 hours, combining water extract, adsorbing by macroporous resin, eluting with water until no purple ring reaction occurs in effluent water, eluting with 70-90% ethanol, collecting eluent, concentrating and drying;
(5) removing alcohol from the alcohol extract obtained by the first method or the water extract obtained by the third method, concentrating, adjusting the pH to 9-14, standing, taking the supernatant, adsorbing by macroporous resin, washing by water or 0.1-30% ethanol, discarding the washing liquid, eluting by 60-90% ethanol, collecting the eluent, concentrating and drying.
When the efficacy test is carried out, the lipid-lowering effect of the eucommia seed oil obtained by refining the crude oil obtained by the eucommia seed oil preparation method (2) and the pharmaceutical composition prepared from the pseudo-ginseng extract obtained by the method (2) in the pseudo-ginseng extract preparation method is the best.
The pharmaceutical composition and pharmaceutically acceptable auxiliary materials can be prepared into preparations such as granules, capsules, tablets, soft capsules, dropping pills and the like.
The pharmaceutical composition can be prepared into soft capsules, and the soft capsules comprise capsule liquid and capsule shells, and are composed of the following components in parts by weight: the capsule solution comprises main drugs and auxiliary materials, wherein the main drugs comprise eucommia seed oil, pseudo-ginseng extract, red yeast powder and propolis, the auxiliary materials comprise vegetable oil and beeswax, the main drugs account for 25% -30% of the capsule solution, and the beeswax accounts for 1.3% -1.7%, preferably 1.5% of the capsule solution in the auxiliary materials; the capsule shell is made from gelatin, glycerol, purified water and titanium dioxide, and the weight ratio of the gelatin: glycerol: purified water: titanium dioxide 1:0.4-0.45:0.9-1.1: 0.05-0.06; wherein the weight ratio of gelatin, glycerol, purified water and titanium dioxide in the capsule shell is preferably gelatin: glycerol: purified water: titanium dioxide 1:0.42:1: 0.06; the weight ratio of the capsule liquid to the capsule shell is: the capsule shell is 5-7:4, preferably 3: 2.
The preparation method of the soft capsule comprises the following steps:
(1) weighing capsule liquid materials: weighing the raw materials of eucommia seed oil, pseudo-ginseng extract, red yeast powder and propolis according to the proportion of the raw materials of the main medicine, and weighing the vegetable oil and the beeswax according to the proportion of the auxiliary materials for later use;
(2) mixing vegetable oil and Cera flava, heating to dissolve Cera flava completely, and mixing to obtain vegetable oil mixed matrix;
(3) adding the propolis obtained in the step (1) into the substrate obtained in the step (2), stirring uniformly, adding the pseudo-ginseng extract, the red yeast powder, the propolis and the eucommia seed oil obtained in the step (1) into the substrate, stirring uniformly, standing at room temperature for cooling, filtering and vacuumizing;
(4) weighing capsule shell materials according to a proportion, melting the capsule shell materials, vacuumizing, and standing while keeping the temperature;
(5) and (4) pelleting, shaping, washing and drying the capsule liquid and the capsule shell materials obtained in the steps (3) and (4).
The pharmaceutical composition can be prepared into dropping pills, which comprise a main material and a substrate, and comprise the following components in parts by weight: the main materials are eucommia seed oil, pseudo-ginseng extract, red yeast powder and propolis, the matrix is PEG4000 and PEG6000, and the weight ratio of the materials is PEG 4000: PEG6000 as 2:7-9, wherein the weight ratio of the main materials to the matrix is as follows: 2:7-9 of matrix; wherein the weight ratio of the matrix is preferably PEG 4000: PEG6000 is 1:4, and the weight ratio of the main material to the matrix is preferably as follows: matrix 1: 4.
The preparation method of the dripping pill comprises the following steps:
(1) preparing materials: accurately weighing the main material and the matrix;
(2) heating and stirring the matrix to a molten state, adding the main material into the molten matrix, and uniformly stirring to obtain a molten mixed liquid medicine for later use;
(3) and (3) putting the liquid medicine obtained in the step (2) into a dropping pot of the dropping pill, wherein the temperature of the liquid medicine is 75-85 ℃, the temperature of cooling liquid dimethyl silicon oil is 8-15 ℃, a dropping head with the dropping opening diameter of 2.5mm is used for dropping into the dimethyl silicon oil at the dropping speed of 30-50 drops/minute with the dropping distance of 3-6cm, and the liquid medicine is obtained after shrinkage into pills, screening and wiping.
The applicant respectively observes the effectiveness and the safety of the pharmaceutical composition of the invention through animal pharmacodynamic tests and toxicological tests, and the preparation steps of tested samples of the tests are as follows:
(1) eucommia seedPreparation of oil: pulverizing semen Eucommiae to 30 mesh, extracting under 40MPa with CO2The flow rate is 20kg/h, the extraction temperature is 15 ℃, the extraction is 3h, the separation pressure is 10MPa, the separation temperature is 40 ℃, the separated eucommia seed oil is obtained by washing, dehydrating, degumming, dewaxing, decoloring, deacidifying and deodorizing and refining, and the content of alpha-linolenic acid oil is measured to be 67.8%;
(2) preparing a pseudo-ginseng extract: reflux-extracting Notoginseng radix coarse powder with 6 times of 70% ethanol for 2 times, each for 2 hr, mixing ethanol extractive solutions, removing ethanol, adsorbing with D101 type macroporous resin, eluting with water until no purple ring reaction appears in effluent water, eluting with 75% ethanol, collecting eluate, concentrating, and drying;
(3) weighing the following raw materials in proportion: 146.4 parts of red yeast powder, 73.2 parts of eucommia seed oil, 14.4 parts of propolis and a pseudo-ginseng extract equivalent to 1000 parts of pseudo-ginseng in crude drug amount;
(4) and (4) uniformly mixing the raw materials in the step (3), and adding purified water to prepare a suspension of 0.3g crude drug/ml.
First, animal drug effect test
1. Material
1.1 animal healthy SPF-grade SD male rats 60, with a weight of 180-: SCXK (xiang) 2011-: SYXK (xiang) 2011-.
1.2 high-fat feed: the formula comprises 1% of cholesterol, 10% of egg yolk powder, 10% of lard, 0.2% of bile salt and 78.8% of common feed. The preparation method comprises adding cholesterol and yolk powder into common feed (pulverizing), mixing, spraying melted adeps Sus Domestica, stirring, and molding. Preparing an address: slaik zoo laboratory, Hunan province.
1.3 drugs and reagents
Test samples were provided by the applicant. The prescription comprises propolis, red yeast rice, eucommia seed oil and pseudo-ginseng extract; 0.30g crude drug/ml, batch number: 20130402. the required concentration is prepared by distilled water during the experiment, and the mixture is shaken up when in use. Lovastatin, produced by Chengdu Yongkang pharmaceuticals, Inc.; production batch number: 20121108, respectively; approval document No.: state of ChinaThe drug standard H10970279. Cholesterol, DH565-1.1, 500g, C27H46O, FW:386.67, available from Beijing Ding national biotechnology, Inc. Egg yolk powder: the commercial Yuxiang food additive is provided by the Ministry of nutrition. Cholesterol kit (lot No. 2401967), triglyceride kit (lot No. 240322), high density lipoprotein kit (lot No. 2402020), low density lipoprotein kit (lot No. 2401319), APOA1 kit (lot No. 22400487), APOB kit (lot No. 22400485), all of which are provided by yapei corporation.
1.4 instruments
KDC-12 centrifuge, Innovation Co., Ltd, science technologies; g100 micropipette (100ul), zhongtai precision instruments ltd; yapec 8000 full-automatic biochemical analyzer (Yapek, USA).
2. Method of producing a composite material
2.1 Experimental methods
Grouping and administering 60 healthy SPF SD male rats with weight of 182.3 +/-1.3 g, cage-feeding, freely taking water, feeding at the temperature of 20-26 ℃ and humidity of 40-70%, adaptively feeding for 3 days, fasting without water prohibition for 12 hours, and taking serum to measure TC, TG, HDL and LDL as blood lipid levels before test. Dividing animals into normal control group, model control group, lovastatin group, and low, medium, and high dosage groups (0.06, 0.12, 0.24 g.kg) according to total cholesterol level-1). Each group contained 10 animals. High fat diet was given to the remaining 5 groups except the normal control group. The intragastric administration is started on the grouping day for prevention. Test sample (low, medium and high) dose groups are respectively set according to 0.06, 0.12 and 0.24 g.kg-13 doses of the test sample for intragastric administration, the positive medicine is 2 g.kg-1And (3) irrigating lovastatin, and irrigating normal control group and model control group with distilled water 1 time per day for 40 days. Weigh once a week. Weighing after fasting for 12h on day 40, collecting blood from orbital vein, and measuring TC, TG, HDL, LDL and APOA in serum1And APOB.
2.2 statistical methods data processing Using EXCEL tables
And (4) showing. And performing difference statistics by using variance analysis of multi-sample mean comparison and q test of pairwise comparison. P <0.05 shows statistical significance.
3 results
3.1 Effect on rat body weight
Before administration, the weight difference of rats in each group has no statistical significance, after model making, the weight of rats in the model group is obviously higher than that of rats in the normal control group (P <0.01), after administration for 40 days, the weight of rats in each administration group does not rise synchronously with that of rats in the model control group, and the weight difference between the tested (medium and high) dose group and the lovastatin group is obviously different from that of rats in the model control group (P < 0.05). See Table 1
TABLE 1 Effect on rat body weight: (
)
Note: comparison with model control group▲P<0.05，▲▲P<0.01；n＝10
3.2 Effect on hyperlipidemia rats TC and TG
Compared with the normal control group, the TC and TG of the model group are obviously increased (P)<0.01), 0.06, 0.12, 0.24 g.kg of test sample to the model control group-1The TC and TG were each reduced differently in the 3 dose groups (P)<0.05) and has the same effect with the lovastatin group, and the two have no obvious difference. See table 2.
3.3 Effect on LDL and HDL in hyperlipidemic rats
The LDL of the model control group was significantly higher than that of the normal control group (P) compared with that of the normal control group<0.01), indicating that the model was successfully replicated, each administration group had a different lowering effect compared to the model control group, in which the test sample was 0.24 g.kg-1The dose group and the lovastatin group have significant difference (P)<0.05); in HDL, the model control group was significantly lower than the normal control group (P)<0.05), compared with a model control group, the administration groups have different degrees of increase but no difference (P is more than 0.05), and the lovastatin group has a significant difference (P) compared with the model group<0.05). See table 2.
TABLE 2 preventive action against blood lipid of experimental hyperlipidemic model rat: (
)
P <0.05, P <0.01, compared to model control; n-10
3.4 Effect on hyperlipidemic rat APOA1 and APOB
The model control group had a significant decrease in APOA1 (P) compared to the normal control group<0.01), APOB is significantly increased (P)<0.01). Compared with the model control group, the lovastatin group has significant effect, and the tested sample is 0.24g/kg-1The statistics of the two groups are different (P)<0.05), other administration groups also have good effect of increasing APOA1, but the difference is not obvious.
APOB was significantly elevated compared to the normal control group (P < 0.01). Compared with the model control group, the administration groups have different degrees of APOB reducing effect and have significant difference through statistical treatment (P < 0.01). See table 3.
TABLE 3 preventive action against blood lipids in experimental hyperlipidemic model rats: (
)
P <0.05, P <0.01, compared to model control; n-10
Second, acute toxicity test
1 materials of the experiment
1.1 medicaments
Test samples were provided by the applicant, the preparation steps of which were:
(1) preparation of eucommia seed oil: pulverizing semen Eucommiae to 30 mesh, extracting under 40MPa with CO2The flow rate is 20kg/h, the extraction temperature is 15 ℃, the extraction is 3h, the separation pressure is 10MPa, the separation temperature is 40 ℃, the separated eucommia seed oil is obtained by washing, dehydrating, degumming, dewaxing, decoloring, deacidifying and deodorizing and refining, and the content of alpha-linolenic acid oil is measured to be 67.8%;
(2) preparing a pseudo-ginseng extract: reflux-extracting Notoginseng radix coarse powder with 6 times of 70% ethanol for 2 times, each for 2 hr, mixing ethanol extractive solutions, removing ethanol, adsorbing with D101 type macroporous resin, eluting with water until no purple ring reaction appears in effluent water, eluting with 75% ethanol, collecting eluate, concentrating, and drying;
(3) weighing the following raw materials in proportion: 146.4 parts of red yeast powder, 73.2 parts of eucommia seed oil, 14.4 parts of propolis and a pseudo-ginseng extract equivalent to 1000 parts of pseudo-ginseng in crude drug amount;
(4) and (4) uniformly mixing the raw materials in the step (3), and adding purified water to prepare a suspension of 0.3g crude drug/ml (maximum concentration).
The daily clinical dose of the product for adults is 0.354g, and distilled water is used for preparing 0.3g crude drug/ml (maximum concentration) for mouse gavage during test.
1.2 animals
18-22 g of ICR mice, clean grade, half male and half female, provided by Changsha Tianjiu biotechnology limited company; production license number of experimental animal: SCXK (Xiang) 2009-0012. The animals are placed in an SPF laboratory for breeding, the room temperature is 20-25 ℃, the relative humidity is 50-70%, and the experimental animals use license numbers: SYXK (xiang) 2011-.
2 method
40 mice were taken and randomly divided into 2 groups: the mice in the administration group are intragastrically administered with a test sample with the maximum concentration of 0.3g/ml (ig) for 0.2ml/20g in maximum volume after fasting (without water) for 14 hours before an experiment, and intragastrically administered with distilled water with the same volume as that in the control group for 3 times at intervals of 4 hours in one day, the cumulative administration dose is 9g/kg, and the behavior and activity, hair color and the like of the animals and the survival condition of the animals in 14 days after the administration are observed every day.
3 results
After 14 days of observation, no death occurred in the two groups of animals, the animals were sacrificed and dissected, no abnormality was observed in the heart, liver, spleen, lung, kidney, etc., and the weight of the animals increased without significant difference from that of the distilled water group (Table 4).
TABLE 4 mouse acute toxicity test results
4 conclusion
In order to observe the toxicity of the test substances, the mice are gavaged at the maximum concentration and the maximum volume, no animal death occurs, and LD cannot be obtained50. The drug is continuously administered for 3 times at intervals of 4 hours within 24 hours, the cumulative dosage (maximum tolerance) of the test object in one day reaches 9g/kg, which is equivalent to 1525 times of the clinical dosage of an adult of 60 kg according to the weight of kg, and the animal recovers to be normal after half an hour except the phenomena of softening stool, weakening of autonomic activity and the like after administration (the animal recovers to be normal after half an hour), so that the drug administration of the test object in the recommended human dosage range is safe.
The inventor conducts a great deal of research on the raw material composition of the hypolipidemic pharmaceutical composition of the invention: in order to screen and verify the necessity and importance of each raw material in the formula and the optimal compatible dosage, the inventor conducts multiple screening researches:
(I) preliminary screening raw materials
The inventor conducts preliminary screening research on various raw materials and the dosage thereof, selects the main raw materials which are selected from monascus powder, cassia seed, ginkgo, salvia miltiorrhiza, polygonum multiflorum, propolis, rhizoma alismatis, apocynum venetum, panax notoginseng, hawthorn, polygonatum odoratum, lotus leaf, poria cocos, schisandra chinensis and polygonum cuspidatum as the alternative in the preliminary screening process, combines the main raw materials with eucommia seed oil for application, and determines each test group to hyperlipidemia by the method under the animal efficacy test item of the hypolipidemic pharmaceutical composition of the inventionRats TC and TG, LDL and HDL, APOA1And the effect of APOB. Each test group was evaluated for the serum TC (Y) of rats1) TG value (Y)2) HDL value (Y)3) LDL value (Y)4)、APOA1Value (Y)5) APOB value (Y)6) Is the influence of (A) as an index, Y1(after test group test TC-before test group TC)/(after test group test TC-before test group TC), Y2Y (TG after test group-TG before test group)/(TG after test group-TG before test group)3= (post-test HDL-test pre-test HDL)/(post-model HDL-model test HDL), Y4(post-test LDL in test group-Pre-test LDL in test group)/(post-test LDL in model group-Pre-test LDL in model group), Y5= (post test APOA of test group)1APOA before the test group test1) /(APOA after model group test)1Model group Pre-test APOA1)，Y6(post-test APOB-pre-test APOB in test group)/(post-test APOB-pre-test APOB in model group), the six indices were each weighted at 1/6, and the composite score Y was 1/6Y1+1/6Y2+1/6Y3+1/6Y4+1/6Y5+1/6Y6. The inventor shows that the combined blood fat reducing effect of the composition is the best result after multiple screening and comprehensive comparison in the table 5.
The dosages of the raw materials in the experiment are respectively as follows: the dosage of eucommia seed oil is 0.08g/kg.bw, the dosage of monascus powder is 0.08g/kg.bw, the dosage of propolis is 0.03g/kg.bw, and the dosages of panax notoginseng, hawthorn, cassia seed, apocynum venetum, rhizoma alismatis, polygonum cuspidatum, ginkgo, salvia miltiorrhiza, polygonum multiflorum, polygonatum odoratum, poria cocos, lotus leaf and schisandra chinensis are 0.9g crude drugs/kg.bw. The test sample of each experimental group is a mixture of the raw materials of the experimental group.
Table 5 raw material composition prescreening table
(II) study of raw Material composition
The single medicinal materials such as red koji powder, eucommia seed oil and the like have many researches on the effect of reducing blood fat, but the deep researches on action targets and mechanisms are few, the inventor conducts composition screening by constructing a complex interaction network between each chemical component in a preselected compound and the lipid-reducing target, combines the preliminary screening result, takes the red koji powder, the eucommia seed oil, the propolis, the pseudo-ginseng, the hawthorn and the polygonum multiflorum as alternative main raw materials, and the orthogonal analysis verifies that the following:
the test groups were tested for TC and TG, LDL and HDL, and APOA in hyperlipidemic rats in the same manner as described above in the animal test of efficacy of the hypolipidemic pharmaceutical composition of the present invention1And the effect of APOB.
Comprises red koji powder, eucommia seed oil and propolis as main raw materials, Polygoni Multiflori radix (10:1 ratio extract, ethanol extract), Notoginseng radix (Notoginseng radix extract containing Notoginseng radix total saponin 93.5%), fructus crataegi (fructus crataegi extract containing total flavone (calculated by rutin) 10.4%) as three factors, and administration and non-administration of drug at two levels (shown in Table 6), and TC value (Y) of rat serum1) TG value (Y)2) HDL value (Y)3) LDL value (Y)4)、APOA1Value (Y)5) APOB value (Y)6) Is the influence of (A) as an index, Y1(after test group test TC-before test group TC)/(after test group test TC-before test group TC), Y2Y (TG after test group-TG before test group)/(TG after test group-TG before test group)3= (post-test HDL-test pre-test HDL)/(post-model HDL-model test HDL), Y4(post-test LDL in test group-Pre-test LDL in test group)/(post-test LDL in model group-Pre-test LDL in model group), Y5= (post test APOA of test group)1APOA before the test group test1) /(APOA after model group test)1Model group Pre-test APOA1)，Y6(post-test APOB-pre-test APOB in test group)/(post-test APOB-pre-test APOB in model group), the six indices were each weighted at 1/6, and the composite score Y was 1/6Y1+1/6Y2+1/6Y3+1/6Y4+1/6Y5+1/6Y6Orthogonal design experiments were performed, see tables 7-8.
The dosages of the raw materials in the experiment are respectively as follows: the dose of monascus powder is 0.08g/kg.bw, the dose of eucommia seed oil is 0.08g/kg.bw, the dose of propolis is 0.03g/kg.bw, the dose of pseudo-ginseng is 0.9g of crude drug/kg.bw, the dose of hawthorn is 0.9g of crude drug/kg.bw, and the dose of polygonum multiflorum is 0.9g of crude drug/kg.bw. The test sample of each experimental group is a mixture of the raw materials of the experimental group.
TABLE 6 orthogonal factor horizon
TABLE 7-1L8(27) Orthogonal test the results of the experiments in each test group (
)(n＝10)
Tables 7 to 2L8(27) Orthogonal test the results of the experiments in each test group (
)(n＝10)
TABLE 8L8(27) Orthogonality test and results
TABLE 9 analysis of variance results
F0.01(1,3)＝34.13 F0.05(1,3)＝10.13 F0.1(1,3)＝5.54
Table 10B × C collocation table
| Factors of the fact | C1 | C2 |
| B1 | (0.7340+0.6370)/2＝0.6855 | (0.6104+0.4668)/2＝0.5386 |
| B2 | (0.8785+0.7871)/2＝0.8328 | (0.6680+0.5398)/2＝0.6039 |
In summary of tables 6-10, the difference values of the raw materials, polygonum multiflorum, hawthorn and pseudo-ginseng, are visually analyzed according to the R values. Analysis of variance shows that hawthorn, pseudo-ginseng and fleece-flower root have extremely obvious influence on the result (P is less than 0.01), the interaction between pseudo-ginseng and fleece-flower root has obvious influence (P is less than 0.05), and the best matching of BC factors in the table 10 is B1C 2. The overall analysis table shows 6-10, the best raw material composition is red koji powder, eucommia seed oil, pseudo-ginseng and propolis, the hawthorn and the polygonum multiflorum have antagonistic action on the red koji powder, the eucommia seed oil and the propolis, and the pseudo-ginseng can synergistically enhance the effect of reducing blood fat.
(III) orthogonal experiment of raw material ratio
Based on the results of the orthogonal design test of raw material selection, the inventors determined the respective test groups for TC and TG, LDL and HDL, and APOA in hyperlipidemic rats in the same manner as described above under the animal efficacy test item of the hypolipidemic pharmaceutical composition of the present invention1And the effect of APOB.
Adding red koji powder, Eucommiae cortex seed oil, Notoginseng radix extract (containing Notoginseng radix total saponin 90.5%, converted into medicinal material), and propolis9(34) Orthogonal assay (Table 11) to obtain TC values (Y) for rat serum1) TG value (Y)2) HDL value (Y)3) LDL value (Y)4)、APOA1Value (Y)5) APOB value (Y)6) Is the influence of (A) as an index, Y1(after test group test TC-before test group TC)/(after test group test TC-before test group TC), Y2Y (TG after test group-TG before test group)/(TG after test group-TG before test group)3= (post-test HDL-test pre-test HDL)/(post-model HDL-model test HDL), Y4(post-test LDL in test group-Pre-test LDL in test group)/(post-test LDL in model group-Pre-test LDL in model group), Y5= (post test APOA of test group)1APOA before the test group test1) /(APOA after model group test)1Model group Pre-test APOA1)，Y6(post-test APOB-pre-test APOB in test group)/(post-test APOB-pre-test APOB in model group), the six indices were each weighted at 1/6, and the composite score Y was 1/6Y1+1/6Y2+1/6Y3+1/6Y4+1/6Y5+1/6Y6See tables 12-13.
The tested sample of each experimental group in the experiment is the mixture of the raw materials of the experimental group, and the dosage of each experimental group is 0.24 g/kg.bw.
TABLE 11 orthogonal factors horizon
TABLE 12-1L9(34) Orthogonal test the results of the experiments in each test group (
)(n＝10)
Note: model No. 10 as model control group
Tables 12-2L9(34) Orthogonal test the results of the experiments in each test group (
)(n＝10)
Note: model No. 10 as model control group
TABLE 13L9(34) Orthogonality test and results
TABLE 14 analysis of variance results
F0.10(2,2)＝9.00 F0.05(2，2)＝19.00 F0.01(2，2)＝99.0
Throughout tables 11-14, factor A (Ginkgo biloba) is statistically significant for differences in outcome. The optimal test scheme A can be known through visual analysis2B1C2D3The inventors tested protocol A2B1C2D3Scheme A3B2C1D3Scheme A3B3C2D1Scheme A2B1C3D2The test is repeated for 10 times, and the test result is verified in the table 15, which shows that the optimal test scheme is A2B1C2D3The compound red rice wine is prepared from 10 parts of red rice powder, 5 parts of eucommia seed oil, 70 parts of pseudo-ginseng and 1 part of propolis which are optimally used as raw materials in a compatible manner.
Table 15 results of orthogonal verification test (n ═ 10)
The inventor conducts fine adjustment on the compatibility, and tests prove that the red yeast rice powder 146.4 parts, the eucommia seed oil 73.2 parts, the propolis 14.4 parts and the pseudo-ginseng raw powder 1000 parts in the examples 1 and 2 are the best compatibility.
Based on the raw material screening and the research on the optimal raw material compatibility, the inventor carries out series research on the dosage form of the pharmaceutical composition, compares the manufacturing process steps, the manufacturing cost, the product stability, the bioavailability and other factors of various dosage forms according to the characteristics of the raw materials, finally selects the dosage form as a dripping pill and a soft capsule, and details on the process research of the dripping pill and the soft capsule are as follows:
(I) research on dropping pill formulation process
(1) Prescription screening
The effective components extracted from the formula of the matrix are mainly water-soluble, so that common water-soluble matrixes (PEG4000) and (PEG6000) are selected, and common cooling agent dimethyl silicone oil is selected. In the test, a dropper with the diameter of 2.5mm is adopted and is made by heat preservation dripping at the temperature of 75-85 ℃, the dripping speed is 30-50 drops/min, the dripping distance is 5.5cm, and the temperature of the cooling liquid is 8-15 ℃. The matrix ratios and the experimental results are shown in Table 16.
TABLE 16 base mix ratio and experimental results
The test result shows that the matrix is PEG 4000: when PEG6000 is 1:4, the mixed matrix and the medicine are easy to fuse, the viscosity is moderate at night, the dripping can be kept uniform and smooth, and the dripping pill can be well formed. Therefore, PEG4000 was selected: PEG6000 as 1:4 is the best mixed matrix.
② when the drop pills with the proportion of the medicine are added into the matrix for dripping, firstly, the medicine is uniformly dispersed in the matrix and mutually fused, then, the drop pills are dripped into the immiscible coolant for condensation and molding, the molding rate is closely related to the uniformity of the medicine dispersion in the matrix, the different proportions in the following table are selected for carrying out the dripping test, and the influence of the different proportions of the medicine and the matrix on the dispersion condition of the medicine in the matrix and the molding condition of the drop pills is examined.
TABLE 17 selection of drug to substrate ratio
Test results show that when the ratio of the medicine to the matrix is 1:4, the medicine and the matrix are easy to mix, the consistency is moderate, the dripping speed is uniform, and the obtained dripping pill is good in forming and smooth in surface. Therefore, the optimal ratio of the selected medicine to the matrix is 1: 4.
(2) Single factor test of forming process
Dropping speed: dripping by using a dropper with the diameter of 2.5mm and the heat preservation temperature of 75-85 ℃, wherein the dripping distance is 5.5cm, the temperature of cooling liquid is 8-15 ℃, and the dripping speeds are compared.
TABLE 18 Effect of different drop velocities on balls
Test results show that when the dripping speed is 30-50 drops/min, the obtained dripping pills have good appearance.
② temperature of condensing agent
TABLE 19 Effect of cooling temperature on pellets
Test results show that when the temperature of the coolant is 8-15 ℃, the obtained dropping pills have good appearance.
③ temperature of the liquid medicine
TABLE 20 influence of temperature of liquid medicine on balls
Test results show that when the dripping temperature is 75-85 ℃, the dripping condition of the dripping pill is better, but the dripping temperature is too high, which affects the chemical components of the substance, so the dripping temperature is selected to be 75-85 ℃.
Drop distance
TABLE 21 Effect of drop spacing on pills
Test results show that when the drop distance is 3-6cm, the obtained dropping pills have good appearance quality.
(3) Package (I)
The traditional Chinese medicine dripping pills are generally easy to absorb moisture, so the traditional Chinese medicine dripping pills are sealed and packaged. The dripping pill is packaged in a glass bottle which is difficult to ventilate and drench so as to avoid the deterioration of the finished product due to moisture absorption in storage.
(4) Process verification
For the verification process, three batches of samples were prepared, and panax notoginseng saponins, lovastatin and linolenic acid were used as indexes for investigation, and the test results are shown in table 22. The three batches of samples are stable in various examinations, and the obtained dripping pills are well formed and round.
Table 22 verification of process results
(II) Soft Capsule formulation Process Studies
(1) Selection of beeswax dosage
In the formula of the product, the pseudo-ginseng extract, the monascus powder and the propolis are powdery substances, the eucommia seed oil is oily substance, and the soybean oil is used as a solvent to be mixed with the raw materials. The suspending agent beeswax is added for ensuring the uniformity and stability of the raw and auxiliary materials during pelleting. The following tests were carried out with the choice of the amount of beeswax: number 1: 30g of pseudo-ginseng extract, 36.6g of red yeast powder, 18.3g of eucommia seed oil, 0.36g of propolis, 3g of beeswax, 208.5g of soybean oil, 2: 30g of pseudo-ginseng extract, 36.6g of red yeast powder, 18.3g of eucommia seed oil, 0.36g of propolis, 4.5g of beeswax and 205.5g of soybean oil, wherein the weight ratio of the pseudo-ginseng extract to the red yeast powder is 3: 30g of pseudo-ginseng extract, 36.6g of monascus powder, 18.3g of eucommia seed oil, 0.36g of propolis, 6g of beeswax and 205.5g of soybean oil, and the test results are as follows:
the total mixture of number 1 had good fluidity and general stability, and was layered after standing for 48 hours.
The total mixture of number 2 has good fluidity and good stability, and no delamination phenomenon after being placed for 48 hours.
The total mixture of number 3 had good stability but slightly poor flowability.
Tests have shown that the greater the amount of suspending agent, the better the stability of the total mixture. When the dosage of the beeswax is 4.5g (1.5%), the layering of the total mixture can be effectively avoided, and the fluidity is good, so that the fluidity of the total mixture is poor and the channel is easy to block if the dosage of the beeswax is continuously increased. Therefore, the dosage of the beeswax is about 1.5 percent.
(2) Determination of mixing time
To determine the mixing time, we performed the following tests, setting the mixing time at 20 minutes, 30 minutes and 40 minutes, sampling 3 times, and determining the content index of the effective component lovastatin, and the results are shown in the following table 23:
TABLE 23
(3) Determination of the setting time
In the process of pressing the soft capsules, the pressed capsules need to be shaped to ensure the appearance of the capsules. The main factors influencing the shaping effect of the capsules in the shaping process lead to the shaping time. We therefore performed the following tests for setting time, as shown in Table 24 below:
watch 24
From the aspects of setting time and pill forming conditions, the setting time is less than 2 hours, the capsule is soft, has adhesion and is not easy to form, the setting time is more than or equal to 2 hours, the capsule has good hand feeling and is good to form, so the setting time is selected to be 2-4 hours.
(4) Process verification
For process verification, three batches of samples were prepared, and pseudo-ginseng saponin R1 and lovastatin were used as indexes for investigation, and the test results are shown in Table 25. All the tests of the three batches of samples are basically stable, and the obtained soft capsules are well formed.
TABLE 25 Process verification results
The invention has the beneficial effects that:
(1) the pharmaceutical composition for reducing blood fat disclosed by the invention adopts red yeast rice fine powder, pseudo-ginseng extract, eucommia seed oil and propolis as main raw materials, and selects the optimal compatibility dosage, the optimal preparation method and the like, and toxicological tests and animal pharmacodynamic tests show that the pharmaceutical composition is safe and effective, and provides a product with reliable curative effect and good blood fat reducing effect.
(2) The pharmaceutical composition is prepared into a soft capsule dosage form, and the preparation process is optimized as follows: the eucommia seed oil in the formula is liquid and contains unsaturated fatty oil, and the prepared soft capsule is convenient to take and transport on one hand, can avoid the problems of medicine dissociation, exudation and the like on the other hand, and ensures the stability and effectiveness of the medicine; in addition, propolis is a fat-soluble medicine, the pseudo-ginseng extract contains more saponin extractum, and the soft capsule dosage form ensures that the extract is well fused and uniformly mixed with eucommia seed oil and propolis; the product has small dosage and is suitable for soft capsule preparation; after the medicine is taken, the content is released rapidly, and the bioavailability is high; simple production equipment, easy operation, small weight difference, low cost, no dust and contribution to labor protection.
(3) The medicine composition is prepared into a dripping pill dosage form, and the preparation process is optimized as follows: the eucommia seed oil is liquid and contains unsaturated fatty oil, and is prepared into the dropping pill, so that the dropping pill is convenient to take and transport on one hand, and on the other hand, the dropping pill can be dissolved with a substrate, the contact area with air is reduced, the dropping pill is not easy to oxidize and volatilize, the substrate is a non-aqueous substance, the hydrolysis is not easy to cause, and the stability and the effectiveness of the medicine are ensured; in addition, propolis is a fat-soluble medicine, the panax notoginseng extract contains more saponin extractum, and the drop pill preparation can well fuse and uniformly mix the panax notoginseng extract, the eucommia seed oil and the propolis and can improve the bioavailability; the product has low dosage, and is suitable for dripping pill preparation; simple production equipment, easy operation, small weight difference, low cost, no dust and contribution to labor protection.
Detailed Description
Example 1 (Soft capsules)
The formula is as follows:
1. and (3) cyst fluid:
1.464kg of red yeast powder (the content of lovastatin is measured to be 0.51%)
0.732kg of eucommia ulmoides seed oil (prepared by pulverizing eucommia ulmoides seed to 40 mesh, extracting under 35MPa, and extracting with CO2The flow rate is 25kg/h, the extraction temperature is 25 ℃, the extraction time is 2.5h, the separation pressure is 8MPa, the separation temperature is 45 ℃, and the separation is carried outWashing the obtained eucommia seed oil with water, dehydrating, degumming, dewaxing, decolorizing, deacidifying, deodorizing and refining to obtain the eucommia seed oil with the alpha-linolenic acid oil content of 67.4 percent
Propolis 0.144kg
1.2kg (equivalent to 10 kg) of Notoginseng radix extract (prepared by reflux-extracting Notoginseng radix coarse powder with 8 times of 70% ethanol for 2 times, each time for 2 hr, mixing ethanol extractive solutions, removing ethanol, adsorbing with D101 type macroporous resin, eluting with water until no purple ring reaction appears in effluent, eluting with 80% ethanol, collecting eluate, concentrating, and drying)
Beeswax 0.2kg
Soybean oil 9.66kg
2. Capsule shell
The preparation method comprises the following steps:
(1) weighing capsule liquid materials: weighing the raw materials of eucommia seed oil, pseudo-ginseng extract, red yeast powder and propolis according to the proportion of the raw materials of the main medicine, and weighing the vegetable oil and the beeswax according to the proportion of the auxiliary materials for later use;
(2) mixing vegetable oil and Cera flava, heating to dissolve Cera flava completely, and mixing to obtain vegetable oil mixed matrix;
(3) adding the propolis obtained in the step (1) into the substrate obtained in the step (2), stirring uniformly, adding the pseudo-ginseng extract, the red yeast powder, the propolis and the eucommia seed oil obtained in the step (1) into the substrate, stirring uniformly, standing at room temperature for cooling, filtering and vacuumizing;
(4) weighing capsule shell materials according to a proportion, melting the capsule shell materials, vacuumizing, and standing while keeping the temperature;
(5) and (4) pelleting, shaping, washing and drying the capsule liquid and the capsule shell materials obtained in the steps (3) and (4).
Example 2 (dropping pill)
Formulation of
1. Main materials:
1.464kg of red yeast powder (the content of lovastatin is measured to be 0.54 percent)
0.732kg of eucommia ulmoides seed oil (prepared by pulverizing eucommia ulmoides seed to 60 mesh, extracting under 40MPa, and extracting with CO2The flow rate is 30kg/h, the extraction temperature is 30 ℃, the extraction is 3h, the separation pressure is 10MPa, the separation temperature is 50 ℃, the separated eucommia seed oil is obtained by washing, dehydrating, degumming, dewaxing, decoloring, deacidifying and deodorizing and refining, and the content of alpha-linolenic acid oil is measured to be 66.5 percent
Propolis 0.144kg
1.2kg (equivalent to 10 kg) of Notoginseng radix extract (prepared by extracting Notoginseng radix coarse powder with 6 times of 75% ethanol under reflux for 3 times, each for 2 hr, mixing ethanol extractive solutions, removing ethanol, adsorbing with D101 type macroporous resin, eluting with water until no purple ring reaction appears in effluent, eluting with 70% ethanol, collecting eluate, concentrating, and drying)
2. Matrix:
PEG4000 2.83kg
PEG6000 11.33kg
method for producing
(1) Preparing materials: accurately weighing the main material and the matrix;
(2) heating and stirring the matrix to a molten state, adding the main material into the molten matrix, and uniformly stirring to obtain a molten mixed liquid medicine for later use;
(3) and (3) putting the liquid medicine obtained in the step (2) into a dropping tank of the dropping pill, wherein the temperature of the liquid medicine is 80 ℃, the temperature of the cooling liquid dimethyl silicone oil is 10 ℃, dropping heads with the dropping opening diameter of 2.5mm are used, the dropping distance is 5cm, the dropping speed is 40 drops/minute, and the liquid medicine is obtained by shrinking into pills, screening and wiping.
Example 3 (Soft capsules)
The formula is as follows:
1. and (3) cyst fluid:
1.464kg of red yeast powder (the content of lovastatin is measured to be 0.51%)
0.732kg of eucommia ulmoides seed oil (prepared by pulverizing eucommia ulmoides seed to 40 mesh, extracting under 35MPa, and extracting with CO2The flow is 25kg/h, the extraction temperature is 25 ℃, the extraction time is 2.5h, the separation pressure is 8MPa, the separation temperature is 45 ℃, and the measured alpha-linolenic acid oil content is 66.1 percent
Propolis 0.144kg
1.32kg (equivalent to 10 kg) of Notoginseng radix extract (prepared by extracting Notoginseng radix coarse powder with 8 times of 70% ethanol under reflux for 2 times, each for 2 hr, mixing extractive solutions, removing ethanol, concentrating, and drying)
Beeswax 0.2kg
Soybean oil 8.8kg
2. Capsule shell
The preparation method comprises the following steps: same as example 1
Example 4 (dropping pill)
Formulation of
1. Main materials:
1.4kg of red yeast powder (the content of lovastatin is measured to be 0.49%)
0.75kg of eucommia ulmoides seed oil (obtained by pulverizing eucommia ulmoides seed to 40 meshes, adding 6 times of cyclohexane by weight, extracting at 25 ℃ for 16min under the microwave power of 800w, distilling the extract under reduced pressure to remove the extractant, washing the obtained eucommia ulmoides seed oil with water, dehydrating, degumming, dewaxing, decolorizing, deacidifying, deodorizing and refining to obtain the eucommia ulmoides seed oil with the alpha-linolenic acid oil content of 68.3%)
Propolis 0.14kg
1.27kg (equivalent to 10.5 kg) of Notoginseng radix extract (prepared by extracting Notoginseng radix coarse powder with 6 times of water for 2 times, each for 2 hr, mixing water extractive solutions, adsorbing with D101 macroporous resin, eluting with water until no purple ring reaction appears in effluent, eluting with 90% ethanol, collecting eluate, concentrating, and drying)
2. Matrix:
PEG4000 2.88kg
PEG6000 12.46kg
the preparation method comprises the following steps: same as example 2
Example 5 (granules)
The formula is as follows:
1.464kg of red yeast powder (the content of lovastatin is measured to be 0.51%)
0.732kg of eucommia ulmoides seed oil (prepared by pulverizing eucommia ulmoides seed to 40 mesh, extracting under 35MPa, and extracting with CO2The flow rate is 25kg/h, the extraction temperature is 25 ℃, the extraction time is 2.5h, the separation pressure is 8MPa, the separation temperature is 45 ℃, the separated eucommia seed oil is obtained by washing, dehydrating, degumming, dewaxing, decolorizing, deacidifying and deodorizing and refining, and the content of alpha-linolenic acid oil is 67.4 percent
Propolis 0.144kg
1.2kg (equivalent to 10 kg) of Notoginseng radix extract (prepared by reflux-extracting Notoginseng radix coarse powder with 8 times of 70% ethanol for 2 times, each time for 2 hr, mixing ethanol extractive solutions, removing ethanol, adsorbing with D101 type macroporous resin, eluting with water until no purple ring reaction appears in effluent, eluting with 80% ethanol, collecting eluate, concentrating, and drying)
The preparation method comprises the following steps: accurately weighing the raw materials, mixing, adding appropriate amount of starch, lactose, and ethanol to obtain soft material, granulating, drying, and grading.
Example 6 (Soft Capsule)
The formula is as follows:
1. and (3) cyst fluid:
1.6kg of red yeast powder (measuring lovastatin content to be 0.52%)
0.65kg of eucommia seed oil (obtained by squeezing eucommia seed at normal temperature, washing the separated crude oil with water, dehydrating, degumming, dewaxing, decolorizing, deacidifying, deodorizing, and refining to obtain a product with an alpha-linolenic acid oil content of 67.3%)
Propolis 0.13kg
1.39kg (equivalent to 11kg crude Notoginseng radix extract) (extracting Notoginseng radix coarse powder with 8 times of 70% ethanol under reflux for 2 times, each for 2 hr, mixing extractive solutions, removing ethanol, concentrating, adjusting pH to 10, standing, collecting supernatant, adsorbing with D101 macroporous resin, washing with 10% ethanol, discarding washing solution, eluting with 80% ethanol, collecting eluate, concentrating, and drying)
Beeswax 0.24kg
Soybean oil 11.50kg
2. Capsule shell
The preparation method comprises the following steps: same as example 1
EXAMPLES 1-6 the pharmaceutical compositions obtained in examples were tested for TC and TG, LDL and HDL, and APOA in hyperlipidemic rats by the same method as described above in the animal test of efficacy of the hypolipidemic pharmaceutical composition of the present invention1And the effect of APOB, the group dosage of each example is 0.24g crude drug/kg.bw, the results are detailed in table 26, and the table shows that the examples 1-6 have better blood fat reducing effect.
TABLE 26-1 EXAMPLES 1-6 test results (
)(n＝10)
P <0.05, P <0.01, compared to model control group
Table 26-2 examples 1-6 test results (
)(n＝10)
P <0.05, P <0.01, compared to model control group
Claims (11)
1. A blood fat reducing pharmaceutical composition is prepared from the following raw materials in parts by weight and pharmaceutically acceptable auxiliary materials:
wherein the content of lovastatin in the red yeast powder is 0.4-0.6%, and the content of alpha-linolenic acid in the eucommia seed oil is 55-75%.
2. The pharmaceutical composition according to claim 1, which is characterized by being prepared from the following raw materials and pharmaceutically acceptable auxiliary materials in parts by weight:
3. the pharmaceutical composition according to claim 1, which is characterized by being prepared from the following raw materials and pharmaceutically acceptable auxiliary materials in parts by weight:
wherein the content of lovastatin in the red yeast powder is 0.45-0.55%, and the content of alpha-linolenic acid in the eucommia seed oil is 60-70%.
4. The pharmaceutical composition according to claim 1, wherein the eucommia seed oil is eucommia seed oil or a mixture of several eucommia seed oils obtained by any one of the following methods:
(1) microwave extraction: crushing eucommia ulmoides seeds to 30-60 meshes, adding an extracting agent with the weight of 5-10 times, extracting for 10-20 min at the extraction temperature of 20-40 ℃ by microwave power of 600-800 w, and removing the extracting agent from an extract through reduced pressure distillation, wherein the extracting agent is cyclohexane or normal hexane or acetone or petroleum ether;
(2) supercritical carbon dioxide extraction: pulverizing eucommia ulmoides seeds to 30-60 meshes, extracting under the pressure of 30-40 MPa and CO2The flow is 20-40 kg/h, the extraction temperature is 15-35 ℃, the extraction time is 1-3 h, the separation pressure is 8-10 MPa, and the separation temperature is 40-50 ℃;
(3) squeezing semen Eucommiae at room temperature, and filtering;
(4) washing the crude oil obtained by the method (1), (2) or (3), dehydrating, degumming, dewaxing, decolorizing, deacidifying, deodorizing and refining.
5. The pharmaceutical composition of claim 1, wherein the notoginseng extract is an extract obtained by any one of the following methods or a mixture of several extracts:
(1) reflux-extracting the pseudo-ginseng coarse powder for 1-3 times by using 4-10 times of 40-75% methanol or ethanol by weight, wherein each time lasts for 1-3 hours, combining ethanol extract, removing ethanol, concentrating and drying;
(2) reflux-extracting the pseudo-ginseng coarse powder for 1-3 times by using 40-75% methanol or ethanol with the weight being 4-10 times of that of the pseudo-ginseng coarse powder, wherein each time lasts for 1-3 hours, merging ethanol extract, removing alcohol, adsorbing by using macroporous resin, eluting by using water until no purple ring reaction occurs in effluent water, eluting by using 70-90% ethanol, collecting eluent, concentrating and drying;
(3) extracting the pseudo-ginseng coarse powder with 4-10 times of water for 1-3 times, each time for 1-3 hours, combining water extract, concentrating and drying;
(4) extracting the pseudo-ginseng coarse powder with 4-10 times of water for 1-3 times, each time for 1-3 hours, combining water extract, adsorbing by macroporous resin, eluting with water until no purple ring reaction occurs in effluent water, eluting with 70-90% ethanol, collecting eluent, concentrating and drying;
(5) removing alcohol from the alcohol extract obtained by the first method or the water extract obtained by the third method, concentrating, adjusting the pH to 9-14, standing, taking the supernatant, adsorbing by macroporous resin, washing by water or 0.1-30% ethanol, discarding the washing liquid, eluting by 60-90% ethanol, collecting the eluent, concentrating and drying.
6. The pharmaceutical composition of any one of claims 1 to 5, prepared into a soft capsule, characterized in that the soft capsule comprises a capsule solution and a capsule shell, and the soft capsule comprises the following components in parts by weight:
the capsule solution comprises main drugs and auxiliary materials, wherein the main drugs comprise eucommia seed oil, pseudo-ginseng extract, red yeast powder and propolis, the auxiliary materials comprise vegetable oil and beeswax, the main drugs account for 25% -30% of the capsule solution, and the beeswax accounts for 1.3% -1.7% of the capsule solution in the auxiliary materials;
the capsule shell is made from gelatin, glycerol, purified water and titanium dioxide, and the weight ratio of the gelatin: glycerol: purified water: titanium dioxide is 1:0.4-0.45:0.9-1.1: 0.05-0.06.
7. The soft capsule of claim 6, wherein the weight ratio of gelatin, glycerol, purified water and titanium dioxide in the capsule shell is gelatin: glycerol: purified water: titanium dioxide is 1:0.42:1: 0.06.
8. The soft capsule according to claim 6, characterized in that it is prepared by the following steps:
(1) weighing capsule liquid materials: weighing the raw materials of eucommia seed oil, pseudo-ginseng extract, red yeast powder and propolis according to the proportion of the raw materials of the main medicine, and weighing the vegetable oil and the beeswax according to the proportion of the auxiliary materials for later use;
(2) mixing vegetable oil and Cera flava, heating to dissolve Cera flava completely, and mixing to obtain vegetable oil mixed matrix;
(3) adding the propolis obtained in the step (1) into the substrate obtained in the step (2), stirring uniformly, adding the pseudo-ginseng extract, the red yeast powder, the propolis and the eucommia seed oil obtained in the step (1) into the substrate, stirring uniformly, standing at room temperature for cooling, filtering and vacuumizing;
(4) weighing capsule shell materials according to a proportion, melting the capsule shell materials, vacuumizing, and standing while keeping the temperature;
(5) and (4) pelleting, shaping, washing and drying the capsule liquid and the capsule shell materials obtained in the steps (3) and (4).
9. The pharmaceutical composition of any one of claims 1 to 5, prepared into dripping pills, characterized in that the dripping pills comprise a main material and a substrate, and comprise the following components in parts by weight:
the main materials are eucommia seed oil, pseudo-ginseng extract, red yeast powder and propolis,
the matrix is PEG4000 and PEG6000, and the weight ratio is PEG 4000: PEG 6000-2: 7-9,
the weight ratio of the main materials to the matrix is as follows: matrix 2: 7-9.
10. The dripping pill according to claim 9, wherein the weight ratio of the base material is PEG 4000: PEG6000 is 1:4, and the weight ratio of the main materials to the matrix is as follows: matrix 1: 4.
11. The dripping pill according to claim 9, characterized by being prepared by the following steps:
(1) preparing materials: accurately weighing the main material and the matrix;
(2) heating and stirring the matrix to a molten state, adding the main material into the molten matrix, and uniformly stirring to obtain a molten mixed liquid medicine for later use;
(3) and (3) putting the liquid medicine obtained in the step (2) into a dropping tank of the dropping pill, wherein the temperature of the liquid medicine is 75-85 ℃, the temperature of cooling liquid dimethyl silicon oil is 8-15 ℃, a dropping head with the dropping opening diameter of 2.5mm is used, the dropping distance is 3-6cm, the liquid medicine is dropped into the dimethyl silicon oil at the dropping speed of 30-50 drops/minute, and the liquid medicine is contracted into pills, screened and wiped to be dry, so that the Chinese medicinal preparation is obtained.
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| CN102219814A (en) * | 2011-05-25 | 2011-10-19 | 河南大学 | Method for extracting aucubin from eucommia ulmoides oliver seed draff |
| CN102994216A (en) * | 2012-11-15 | 2013-03-27 | 山西五台山沙棘制品有限公司 | Method for extracting eucommia seeds through supercritical CO2 extraction |
| CN103169765A (en) * | 2013-03-26 | 2013-06-26 | 汉中永杨医药科技发展有限公司 | Eucommia ulmoides seed oil and red rice compound soft capsule preparation and preparation method thereof |
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2014
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101002825A (en) * | 2007-01-11 | 2007-07-25 | 西北农林科技大学 | Method for preparing Duzhong soft capsule rich in alpha-linolenic acid and effective component of bark of eucommia |
| CN101428117A (en) * | 2008-12-04 | 2009-05-13 | 雷双富 | Medicament for invigorating pulse and reducing adipose, and preparation method thereof |
| CN102219814A (en) * | 2011-05-25 | 2011-10-19 | 河南大学 | Method for extracting aucubin from eucommia ulmoides oliver seed draff |
| CN102994216A (en) * | 2012-11-15 | 2013-03-27 | 山西五台山沙棘制品有限公司 | Method for extracting eucommia seeds through supercritical CO2 extraction |
| CN103169765A (en) * | 2013-03-26 | 2013-06-26 | 汉中永杨医药科技发展有限公司 | Eucommia ulmoides seed oil and red rice compound soft capsule preparation and preparation method thereof |
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